title: Novel quinoxaline 1,4-di-N-oxide derivatives as new potential antichagasic agents.
abstract: As a continuation of our research and with the aim of obtaining new agents against Chagas disease, an extremely neglected disease which threatens 100 million people, eighteen new quinoxaline 1,4-di-N-oxide derivatives have been synthesized following the Beirut reaction. The synthesis of the new derivatives was optimized through the use of a new and more efficient microwave-assisted organic synthetic method. The new derivatives showed excellent in vitro biological activity against Trypanosoma cruzi. Compound 17, which was substituted with fluoro groups at the 6- and 7-positions of the quinoxaline ring, was the most active and selective in the cytotoxicity assay. The electrochemical study showed that the most active compounds, which were substituted by electron-withdrawing groups, possessed a greater ease of reduction of the N-oxide groups.
authors.affiliation: Neglected Diseases Section, Drug R&D Unit, Center for Applied Pharmacobiology Research, University of Navarra, C/Irunlarrea 1, 31008 Pamplona, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Torres
authors.forename: Elsa
authors.initials: E
authors.lastname: Moreno-Viguri
authors.forename: Silvia
authors.initials: S
authors.lastname: Galiano
authors.forename: Goutham
authors.initials: G
authors.lastname: Devarapally
authors.forename: Philip W
authors.initials: PW
authors.lastname: Crawford
authors.forename: Amaia
authors.initials: A
authors.lastname: Azqueta
authors.forename: Leire
authors.initials: L
authors.lastname: Arbillaga
authors.forename: Javier
authors.initials: J
authors.lastname: Varela
authors.forename: Estefanía
authors.initials: E
authors.lastname: Birriel
authors.forename: Rossanna
authors.initials: R
authors.lastname: Di Maio
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy*; D004563:Electrochemistry; D051379:Mice; D016296:Mutagenesis / Q000187:drug effects; D010087:Oxides / Q000737:chemistry*; D011810:Quinoxalines / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D010087:Oxides; D011810:Quinoxalines
keywords: 2-aminofluorene; 4-NPD; 4-nitro-o-phenylendiamine; AF; BFX; Bnz; Chagas disease; Cytotoxicity; Fc; GM; IC(50); Mutagenicity; NR; Nfx; Nifurtimox; PGI; Quinoxaline 1,4-di-N-oxide; Reduction potential; SI; T. cruzi; TBAP; Trypanosoma cruzi; benznidazole; benzofuroxan; concentration for 50% growth inhibition; ferrocene; glucose minimal; number of revertants; percentage of growth inhibition; selectivity index; tetrabutylammonium perchlorate